Variant 5-122152070-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207317.3(ZNF474):c.80T>A(p.Ile27Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,200 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

ZNF474
NM_207317.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

ZNF474 (HGNC:23245): (zinc finger protein 474) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF474 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019510716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF474	NM_207317.3 linkuse as main transcript	c.80T>A	p.Ile27Asn	missense_variant	2/2	ENST00000296600.5	NP_997200.1
ZNF474-AS1	XR_007058915.1 linkuse as main transcript	n.272-1467A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF474	ENST00000296600.5 linkuse as main transcript	c.80T>A	p.Ile27Asn	missense_variant	2/2	1	NM_207317.3	ENSP00000296600
	ENST00000504829.1 linkuse as main transcript	n.233+2554A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00168

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000724

AC:

182

AN:

251302

Hom.:

AF XY:

0.000810

AC XY:

110

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00139

AC:

2032

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

979

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00166

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152332

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00168

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000869

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.000782

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.80T>A (p.I27N) alteration is located in exon 2 (coding exon 1) of the ZNF474 gene. This alteration results from a T to A substitution at nucleotide position 80, causing the isoleucine (I) at amino acid position 27 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0056

T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.049

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

0.56

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.48

N;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

0.0010

B;.;.

Vest4

0.63

MVP

0.12

MPC

0.0082

ClinPred

0.050

GERP RS

3.7

Varity_R

0.32

gMVP

0.041

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over